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Background and Objectives: Administrative data are invaluable for assessing outcomes at the population level. However, there are few validated patient-centered outcome measures that capture morbidity following traumatic brain injury (TBI) using these data. We sought to characterize and validate days at home (DAH) as a measure to quantify population-level outcomes after moderate to severe TBI. We additionally assessed the earliest feasible outcome assessment period for patients with TBI using this outcome measure., Methods: This multicenter retrospective cohort study used linked health administrative data sources to identify adults with moderate to severe TBI presenting to trauma centers in Ontario, Canada, between 2009 and 2021. DAH at 180 days (DAH 180 days ) reflects the total number of days spent alive and at home excluding the days spent institutionalized across care settings. Construct validity was determined using hierarchical quantile regression to assess the associations between clinical and injury covariates with DAH 180 days . Predictive validity was assessed using Spearman rank correlation. We estimated minimally important difference (MID) in DAH 180 days to aid with outcome measure interpretability., Results: There were 6,340 patients who met inclusion criteria. Median DAH 180 days was 70 days (interquartile range 0-144). Mortality occurred in 2,162 (34.1%) patients within 90 days following injury. Patients in the lower DAH 180 days group were more commonly older (absolute standardized difference [ASD] = 0.68) with higher preinjury health resource utilization (ASD = 0.36) and greater injury severity (ASD = 0.81). Increased baseline health resource utilization (-10.1 days, 95% CI -17.4 to -2.8, p = 0.0041), older age (-4.6 days, 95% CI -5.7 to -3.4, p < 0.001), higher cranial injury severity (-84.6 days, 95% CI -98.3 to -71.0, p < 0.001), and major extracranial injuries (-14.2 days, 95% CI -19.5 to -8.93, p < 0.001) were significantly associated with fewer DAH 180 days . DAH 180 days was positively correlated with DAH at up to 3 years ( r = 0.91, 95% CI 0.90-0.92) and negatively correlated with direct health care expenditure ( r s = -0.89, 95% CI -0.88 to -0.90). The average MID estimated from anchor-based and distribution-based methods was 18 days., Discussion: We validate DAH 180 days as a potentially useful outcome measure with construct, predictive, and face validity in a population with moderate to severe TBI. Given the intensity of acute care requirements for patients with TBI, our work highlights DAH 180 days as a feasible and sufficiently responsive outcome measure.

Background: Hospital-acquired (HAP) and ventilator-associated pneumonia (VAP) are important complications early (<30 days) after lung transplantation (LT). However, current incidence, associated factors, and outcomes are not well reported., Methods: LT recipients transplanted at our institution (July 2019-January 2020 and October 2021-November 2022) were prospectively included. We assessed incidence and presentation of pneumonia and evaluated the impact of associated factors using regression models. We also evaluated molecular relatedness of respiratory pathogens collected peri-transplant and at pneumonia occurrence using pulsed-field gel electrophoresis (PFGE)., Results: In the first 30 days post-LT, 25/270 (9.3%) recipients were diagnosed with pneumonia (68% [17/25] VAP; 32% [8/25] HAP). Median time to pneumonia was 11 days (IQR, 7-13); 49% (132/270) of donor and 16% (44/270) of recipient respiratory peri-transplant cultures were positive. However, pathogens associated with pneumonia were not genetically related to either donor or recipient cultures at transplant, as determined by PFGE. Diagnosed pulmonary hypertension (HR, 4.42; 95% CI, 1.62-12.08) and immunosuppression use (HR, 2.87; 95% CI, 1.30-6.56) were pre-transplant factors associated with pneumonia. Pneumonia occurrence was associated with longer hospital stay (HR, 5.44; 95% CI, 2.22-13.37) and VAP with longer ICU stay (HR, 4.31; 95% CI, 1.73-10.75) within the first 30 days post-transplantation; 30- and 90-day mortality were similar., Conclusions: Prospectively assessed early pneumonia incidence occurred in ∼10% of LT. Populations at increased risk for pneumonia occurrence include LT with pre-transplant pulmonary hypertension and pre-transplant immunosuppression. Pneumonia was associated with increased healthcare use, highlighting the need for further improvements by preferentially targeting higher-risk patients., Competing Interests: Potential conflicts of interest. L. d. S. has received institutional and CIHR research grants and holds a patent unrelated to this study. T. M. reports payments for expert testimony by various legal firms, travel support by Hologic, as well as participation on advisory boards for Merck and Pfizer. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Rationale: Despite the potential risks associated with sedation, there is a paucity of pharmacokinetic/pharmacodynamic (PK/PD) data for propofol and fentanyl in patients supported with veno-venous extracorporeal membrane oxygenation (V-V ECMO)., Objective: Describe propofol and fentanyl PK/PD profiles in V-V ECMO patients., Methods and Measurements: Prospective, single-center, open-label PK/PD study at the Toronto General Hospital ICU between July 2022 and January 2023. Using high-performance liquid chromatography-tandem mass spectrometry, propofol and fentanyl total concentrations were measured during V-V ECMO. Sequential PK/PD modeling, using sex as a covariate, was conducted with processed electroencephalography (PSI) for sedation, and expiratory occlusion pressure (P occ ), and airway occlusion pressure during the first 0.1 seconds (P 0.1 ) for respiratory effort., Main Results: Eleven patients underwent 106 evaluations over a median (IQR) follow-up of 146 (116-146) hours. Patient's average (±SD) age was 43 (±13) years, and 55% were female. Propofol and fentanyl PK were best described by a two-compartment model. Propofol-PSI PD was described using an effect compartment, with a coefficient of determination (ρ 2 ) of 0.78. There was a significant increase in propofol ( p =0.01) and fentanyl ( p =0.03) clearance within 10 minutes of ECMO initiation, plateauing after 8 hours of ECMO support. Despite this, patient over-sedation (PSI<40) occurred in 74% of the observations. Females exhibited higher sedative central volume of distribution and lower propofol clearance., Conclusion: ECMO initiation resulted in a time-limited increased sedative clearance. PSI accurately described sedative PD, but variable respiratory effort was observed irrespective of sedative plasma concentrations. Sex-based differences were found in sedative PK/PD parameters.

Point of Care ultrasound (POCUS) of the lungs, also known as lung ultrasound (LUS), has emerged as a technique that allows for the diagnosis of many respiratory pathologies with greater accuracy and speed compared to conventional techniques such as chest x-ray and auscultation. The goal of this narrative review is to provide a simple and practical approach to LUS for critical care, pulmonary, and anesthesia providers, as well as respiratory therapists and other health care providers to be able to implement this technique into their clinical practice. In this review, we will discuss the basic physics of LUS, provide a hands-on scanning technique, describe LUS findings seen in normal and pathological conditions (such as mainstem intubation, pneumothorax, atelectasis, pneumonia, aspiration, COPD exacerbation, cardiogenic pulmonary edema, ARDS, and pleural effusion) and also review the training necessary to achieve competence in LUS., (© 2024. The Author(s).)

Background: Inspiratory threshold loading (ITL) and associated dyspnoea have been shown to interfere with cognition during cognitive-motor dual tasking. However, ITL has not been compared with another rhythmic muscle activity, such as lower limb pedalling. While ITL has been shown to interfere with cognition, the mechanism of the prefrontal cortex (PFC) during ITL or other rhythmical muscle dual tasking, has not been elucidated. Given the cognitive interference that arises during ITL, we hypothesise that ITL cognitive-motor dual tasking will result in greater cognitive decrements and increased PFC activity compared with the pedalling cognitive-motor dual task., Methods: 30 healthy participants (16 females; median age 23 (interquartile range 23-24) years) were recruited. They performed five 3-min tasks in a single visit in a random order: single tasks were ITL, pedalling and Stroop task and dual tasks were ITL-Stroop and pedalling-Stroop. Participant's PFC activity was assessed bilaterally using functional near-infrared spectroscopy throughout each task. Single- and dual-task cognitive performance was evaluated by measuring Stroop task reaction time and accuracy. Dyspnoea and rating of perceived exertion were evaluated at the end of each task., Results: ITL-Stroop resulted in greater impairments in reaction time (p<0.001), accuracy (p<0.01) and increased medial/dorsolateral PFC activity (p≤0.006) than pedalling-Stroop. ITL-Stroop elicited greater Borg dyspnoea and rating of perceived exertion than pedalling-Stroop (p<0.001), despite pedalling-Stroop having a greater heart rate response (p<0.001)., Conclusion: The heightened cognitive decrements, perceptual response and PFC activity suggest that inspiratory muscle loading and its accompanied dyspnoea results in greater cognitive interference than rhythmic pedalling., Competing Interests: Conflict of interest: None declared., (Copyright ©The authors 2024.)

Background: Sigh breaths may impact outcomes in acute hypoxemic respiratory failure (AHRF) during assisted mechanical ventilation. We investigated whether sigh breaths may impact mortality in predefined subgroups of patients enrolled in the PROTECTION multicenter clinical trial according to: 1.the physiological response in oxygenation to Sigh (responders versus non-responders) and 2.the set levels of positive end-expiratory pressure (PEEP) (High vs. Low-PEEP). If mortality differed between Sigh and No Sigh, we explored physiological daily differences at 7-days., Results: Patients were randomized to pressure support ventilation (PSV) with Sigh (Sigh group) versus PSV with no sigh (No Sigh group). (1) Sighs were not associated with differences in 28-day mortality in responders to baseline sigh-test. Contrarily-in non-responders-56 patients were randomized to Sigh (55%) and 28-day mortality was lower with sighs (17%vs.36%, log-rank p = 0.031). (2) In patients with PEEP > 8cmH 2 O no difference in mortality was observed with sighs. With Low-PEEP, 54 patients were randomized to Sigh (48%). Mortality at 28-day was reduced in patients randomised to sighs (13%vs.31%, log-rank p = 0.021). These findings were robust to multivariable adjustments. Tidal volume, respiratory rate and ventilatory ratio decreased with Sigh as compared with No Sigh at 7-days. Ventilatory ratio was associated with mortality and successful extubation in both non-responders and Low-PEEP., Conclusions: Addition of Sigh to PSV could reduce mortality in AHRF non-responder to Sigh and exposed to Low-PEEP. Results in non-responders were not expected. Findings in the low PEEP group may indicate that insufficient PEEP was used or that Low PEEP may be used with Sigh. Sigh may reduce mortality by decreasing physiologic dead space and ventilation intensity and/or optimizing ventilation/perfusion mismatch., Clinical Trial Registration: ClinicalTrials.gov; Identifier: NCT03201263., (© 2024. The Author(s).)

Background: We previously showed in animals that transpulmonary driving pressure (PL) can be estimated during Neurally Adjusted Ventilatory Assist (NAVA) and Neural Pressure Support (NPS) using a single lower assist maneuver (LAM). The aim of this study was to test the LAM-based estimate of PL (PL&#95;LAM) in patients with acute respiratory failure., Methods: This was a prospective, physiological, and interventional study in intubated patients with acute respiratory failure. During both NAVA and simulated NPS (high and low levels of assist), a LAM was performed every 3 min by manually reducing the assist to zero for one single breath (by default, ventilator still provides 2 cmH 2 O). Following NAVA and NPS SIM periods, patients were sedated and passively ventilated in volume control and pressure control ventilation, to obtain PL during controlled mechanical ventilation (PL&#95;CMV). PL using an esophageal balloon (PL&#95;Pes) was also compared to PL&#95;LAM and PL&#95;CMV. We measured diaphragm electrical activity (Edi), ventilator pressure (PVent), esophageal pressure (Pes) and tidal volume. PL&#95;LAM and PL&#95;Pes were compared to themselves, and to PL&#95;CMV for matching flows and volumes., Results: Ten patients were included in the study. For the group, PL&#95;LAM was closely similar to PL&#95;CMV, with a high correlation (R 2  = 0.88). Bland-Altman analysis revealed a low Bias of 0.28 cmH 2 O, and 1.96SD of 5.26 cmH 2 O. PL&#95;LAM vs PL&#95;Pes were also tightly related (R 2  = 0.77)., Conclusion: This physiological study in patients confirms our previous pre-clinical data that PL&#95;LAM is as good an estimate as PL&#95;Pes to determine PL, in spontaneously breathing patients on assisted mechanical ventilation. Trial registration The study was registered at clinicaltrials.gov (ID NCT05378802) on November 6, 2021., (© 2024. The Author(s).)

The European Society of Intensive Care Medicine (ESICM) has developed evidence-based recommendations and expert opinions about end-of-life (EoL) and palliative care for critically ill adults to optimize patient-centered care, improving outcomes of relatives, and supporting intensive care unit (ICU) staff in delivering compassionate and effective EoL and palliative care. An international multi-disciplinary panel of clinical experts, a methodologist, and representatives of patients and families examined key domains, including variability across countries, decision-making, palliative-care integration, communication, family-centered care, and conflict management. Eight evidence-based recommendations (6 of low level of evidence and 2 of high level of evidence) and 19 expert opinions were presented. EoL legislation and the importance of respecting the autonomy and preferences of patients were given close attention. Differences in EoL care depending on country income and healthcare provision were considered. Structured EoL decision-making strategies are recommended to improve outcomes of patients and relatives, as well as staff satisfaction and mental health. Early integration of palliative care and the use of standardized tools for symptom assessment are suggested for patients at high risk of dying. Communication training for ICU staff and printed communication aids for families are advocated to improve outcomes and satisfaction. Methods for enhancing family-centeredness of care include structured family conferences and culturally sensitive interventions. Conflict-management protocols and strategies to prevent burnout among healthcare professionals are also considered. The work done to develop these guidelines highlights many areas requiring further research., (© 2024. The Author(s).)

Purpose: The aim of this study was to compare the effect of a pressure-controlled strategy allowing non-synchronised unassisted spontaneous ventilation (PC-SV) to a conventional volume assist-control strategy (ACV) on the outcome of patients with acute respiratory distress syndrome (ARDS)., Methods: Open-label randomised clinical trial in 22 intensive care units (ICU) in France. Seven hundred adults with moderate or severe ARDS (PaO 2 /FiO 2  < 200 mmHg) were enrolled from February 2013 to October 2018. Patients were randomly assigned to PC-SV (n = 348) or ACV (n = 352) with similar objectives of tidal volume (6 mL/kg predicted body weight) and positive end-expiratory pressure (PEEP). Paralysis was stopped after 24 h and sedation adapted to favour patients' spontaneous ventilation. The primary endpoint was in-hospital death from any cause at day 60., Results: Hospital mortality [34.6% vs 33.5%, p = 0.77, risk ratio (RR) = 1.03 (95% confidence interval [CI] 0.84-1.27)], 28-day mortality, as well as the number of ventilator-free days and organ failure-free days at day 28 did not differ between PC-SV and ACV groups. Patients in the PC-SV group received significantly less sedation and neuro-muscular blocking agents than in the ACV group. A lower proportion of patients required adjunctive therapy of hypoxemia (including prone positioning) in the PC-SV group than in the ACV group [33.1% vs 41.3%, p = 0.03, RR = 0.80 (95% CI 0.66-0.98)]. The incidences of pneumothorax and refractory hypoxemia did not differ between the groups., Conclusions: A strategy based on PC-SV mode that favours spontaneous ventilation reduced the need for sedation and adjunctive therapies of hypoxemia but did not significantly reduce mortality compared to ACV with similar tidal volume and PEEP levels., (© 2024. The Author(s).)

Background: Imbalances between hospital caseload and care resources that strained U.S. hospitals during the pandemic have persisted after the pandemic amid ongoing staff shortages. Understanding which hospital types were more resilient to pandemic overcrowding-related excess deaths may prioritize patient safety during future crises., Objective: To determine whether hospital type classified by capabilities and resources (that is, extracorporeal membrane oxygenation [ECMO] capability, multiplicity of intensive care unit [ICU] types, and large or small hospital) influenced COVID-19 volume-outcome relationships during Delta wave surges., Design: Retrospective cohort study., Setting: 620 U.S. hospitals in the PINC AI Healthcare Database., Participants: Adult inpatients with COVID-19 admitted July to November 2021., Measurements: Hospital-months were ranked by previously validated surge index (severity-weighted COVID-19 inpatient caseload relative to hospital bed capacity) percentiles. Hierarchical models were used to evaluate the effect of log-transformed surge index on the marginally adjusted probability of in-hospital mortality or discharge to hospice. Effect modification was assessed for by 4 mutually exclusive hospital types., Results: Among 620 hospitals recording 223 380 inpatients with COVID-19 during the Delta wave, there were 208 ECMO-capable, 216 multi-ICU, 36 large (≥200 beds) single-ICU, and 160 small (<200 beds) single-ICU hospitals. Overall, 50 752 (23%) patients required admission to the ICU, and 34 274 (15.3%) died. The marginally adjusted probability for mortality was 5.51% (95% CI, 4.53% to 6.50%) per unit increase in the log surge index (strain attributable mortality = 7375 [CI, 5936 to 8813] or 1 in 5 COVID-19 deaths). The test for interaction showed no difference ( P  = 0.32) in log surge index-mortality relationship across 4 hospital types. Results were consistent after excluding transferred patients, restricting to patients with acute respiratory failure and mechanical ventilation, and using alternative strain metrics., Limitation: Residual confounding., Conclusion: Comparably detrimental relationships between COVID-19 caseload and survival were seen across all hospital types, including highly advanced centers, and well beyond the pandemic's learning curve. These lessons from the pandemic heighten the need to minimize caseload surges and their effects across all hospital types during public health and staffing crises., Primary Funding Source: Intramural Research Program of the National Institutes of Health Clinical Center., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M24-0869.

Extubation represents an essential component of airway management. While being a common procedure in anesthesiology and critical care medicine, it is accompanied by a significant risk of morbidity and mortality. Safe extubation requires considerable skills, risk stratification and advanced planning. It is important to emphasize that intentional extubation is always an elective procedure, and as such should only be executed when conditions are optimal. The purpose of this review is to discuss the complications associated with planned extubation in the adult patient, including risk factors and management strategies, mainly focusing on the postoperative setting., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Sedative overdoses pose a risk of delirium among patients in the ICU, with potential mitigation through the use of a processed EEG monitor (the bispectral index [BIS]) to guide depth of sedation., Research Question: Can BIS-guided deep sedation (Richmond Agitation Sedation Scale [RASS] score, -4 or -5) reduce sedative dosage and increase delirium-free and coma-free (DFCF) days?, Study Design and Methods: A randomized controlled trial was conducted in a tertiary mixed ICU, enrolling patients requiring deep sedation for > 8 h. Patients were assigned randomly to either the clinical assessment (CA) or BIS groups (BIS range, 40-60). Both groups used a BIS sensor, whereas the CA group's screen remained covered. After deep sedation, BIS sensors were removed, and delirium was assessed twice daily by researchers masked to the randomization. The primary outcome was the number of DFCF days within 14 days after deep sedation. Additionally, we compared doses of sedative drugs and BIS values during deep sedation., Results: Ninety-nine patients were included in the study. We found no significant difference in DFCF days (P = .1) between CA and BIS arms, but propofol doses were significantly lower in the BIS group (CA group, 1.77 mg/kg/h [95% CI, 1.60-1.93] vs BIS group, 1.44 mg/kg/h [95% CI, 1.04-1.83]; P = .03). During deep sedation, the CA group spent 46% of the total hours (95% CI, 35%-57%) with BIS values of < 40, whereas the BIS group spent 32% (95% CI, 25%-40%; P = .03). Subgroup analysis focusing on patients sedated for > 24 h revealed an increase in DFCF days in the BIS group (CA group: median, 1 day [interquartile range, 0-9 days] vs BIS group: median, 8 days [interquartile range, 0-13 days]; P = .04)., Interpretation: In this study, BIS-guided deep sedation did not improve DFCF days, but did reduce sedative drug use. In patients requiring sedation for > 24 h, it showed an improvement in DFCF days., Trial Registry: ClinicalTrials.gov; No.: NCT03840577; URL: www., Clinicaltrials: gov., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: The last national estimates of US ICU physician staffing are 25 years old and lack information about interprofessional teams., Research Question: How are US adult ICUs currently staffed?, Study Design and Methods: We conducted a cross-sectional survey (May 4, 2022-February 2, 2023) of adult ICU clinicians (targeting nurse/physician leadership) contacted using 2020 American Hospital Association (AHA) database information and, secondarily, through professional organizations. The survey included questions about interprofessional ICU staffing availability and roles at steady state (pre-COVID-19). We linked survey data to hospital data in the AHA database to create weighted national estimates by extrapolating ICU staffing data to nonrespondent hospitals based on hospital characteristics., Results: The cohort consisted of 596 adult ICUs (response rates: AHA contacts: 2.1%; professional organizations: unknown) with geographic diversity and size variability (median, 20 beds; interquartile range, 12-25); most cared for mixed populations (414 [69.5%]), yet medical (55 [9.2%]), surgical (70 [11.7%]), and specialty (57 [9.6%]) ICUs were well represented. A total of 554 (93.0%) had intensivists available, with intensivists covering all patients in 75.6% of these and onsite 24 h/d in one-half (53.3% weekdays; 51.8% weekends). Of all ICUs, 69.8% had physicians-in-training and 77.7% had nurse practitioners/physician assistants. For patients on mechanical ventilation, nurse to patient ratios were 1:2 in 89.6% of ICUs. Clinical pharmacists were available in 92.6%, and respiratory therapists were available in 98.8%. We estimated 85.1% (95% CI, 85.7%-84.5%) of hospitals nationally had ICUs with intensivists, 51.6% (95% CI, 50.6%-52.5%) had physicians-in-training, 72.1% (95% CI, 71.3%-72.9%) had nurse practitioners/physician assistants, 98.5% (95% CI, 98.4%-98.7%) had respiratory therapists, and 86.9% (95% CI, 86.4%-87.4%) had clinical pharmacists. For patients on mechanical ventilation, 86.4% (95% CI, 85.8%-87.0%) used 1:2 nurses/patients., Interpretation: We found that intensivist presence in adult US ICUs has greatly increased over 25 years. Intensivists, respiratory therapists, and clinical pharmacists are commonly available, and each nurse usually provides care for two patients on mechanical ventilation. However, team composition and workload vary., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: H. B. G. received funds from Gilead Sciences, Inc to serve as a scientific advisor regarding COVID-19 therapeutics and is currently Editor in Chief of CHEST Critical Care. None declared (A. G., D. K. C., A. L. D., R. F., A. A. K., V. X. L., D. L., D. C. S., H. W.)., (Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Clinical management of persons with disorders of consciousness (DoC) is dedicated largely to optimizing recovery. However, selecting a measure to evaluate the extent of recovery is challenging because few measures are designed to precisely assess the full range of potential outcomes, from prolonged DoC to return of preinjury functioning. Measures that are designed specifically to assess persons with DoC are often performance-based and only validated for in-person use. Moreover, there are no published recommendations addressing which outcome measures should be used to evaluate DoC recovery. The resulting inconsistency in the measures selected by individual investigators to assess outcome prevents comparison of results across DoC studies. The National Institute of Neurological Disorders and Stroke (NINDS) common data elements (CDEs) is an amalgamation of standardized variables and tools that are recommended for use in studies of neurologic diseases and injuries. The Neurocritical Care Society Curing Coma Campaign launched an initiative to develop CDEs specifically for DoC and invited our group to recommend CDE outcomes and endpoints for persons with DoCs., Methods: The Curing Coma Campaign Outcomes and Endpoints CDE Workgroup, consisting of experts in adult and pediatric neurocritical care, neurology, and neuroscience, used a previously established five-step process to identify and select candidate CDEs: (1) review of existing NINDS CDEs, (2) nomination and systematic vetting of new CDEs, (3) CDE classification, (4) iterative review and approval of panel recommendations, and (5) development of case report forms., Results: Among hundreds of existing NINDS outcome and endpoint CDE measures, we identified 20 for adults and 18 for children that can be used to assess the full range of recovery from coma. We also proposed 14 new outcome and endpoint CDE measures for adults and 5 for children., Conclusions: The DoC outcome and endpoint CDEs are a starting point in the broader effort to standardize outcome evaluation of persons with DoC. The ultimate goal is to harmonize DoC studies and allow for more precise assessment of outcomes after severe brain injury or illness. An iterative approach is required to modify and adjust these outcome and endpoint CDEs as new evidence emerges., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Purpose of Review: To highlight the emerging crisis of critically ill elderly patients and review the unique burden of multidimensional morbidity faced by these patients and caregivers and potential interventions., Recent Findings: Physical, psychological, and cognitive sequelae after critical illness are frequent, durable, and robust across the international ICU outcome literature. Elderly patients are more vulnerable to the multisystem sequelae of critical illness and its treatment and the resultant multidimensional morbidity may be profound, chronic, and significantly affect functional independence, transition to the community, and quality of life for patients and families. Recent data reinforce the importance of baseline functional status, health trajectory, and chronic illness as key determinants of long-term functional disability after ICU. These risks are even more pronounced in older patients., Summary: The current article is an overview of the outcomes of older survivors of critical illness, putative interventions to mitigate the long-term morbidity of patients, and the consequences for families and caregivers. A multimodal longitudinal approach designed to follow patients for one or more years may foster a better understanding of multidimensional morbidity faced by vulnerable older patients and families and provides a detailed understanding of recovery trajectories in this unique population to optimize outcome, goals of care directives, and ongoing informed consent to ICU treatment., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Topic Importance: Cognitive and physical limitations are common in individuals with chronic lung diseases, but their interactions with physical function and activities of daily living are not well characterized. Understanding these interactions and potential contributors may provide insights on disability and enable more tailored rehabilitation strategies., Review Findings: This review summarizes a 2-day meeting of patient partners, clinicians, researchers, and lung associations to discuss the interplay between cognitive and physical function in people with chronic lung diseases. This report covers four areas: (1) cognitive-physical limitations in patients with chronic lung diseases; (2) cognitive assessments; (3) strategies to optimize cognition and motor control; and (4) future research directions. Cognitive and physical impairments have multiple effects on quality of life and daily function. Meeting participants acknowledged the need for a standardized cognitive assessment to complement physical assessments in patients with chronic lung diseases. Dyspnea, fatigue, and age were recognized as important contributors to cognition that can affect motor control and daily physical function. Pulmonary rehabilitation was highlighted as a multidisciplinary strategy that may improve respiratory and limb motor control through neuroplasticity and has the potential to improve physical function and quality of life., Summary: There was consensus that cognitive function and the cognitive interference of dyspnea in people with chronic lung diseases contribute to motor control impairments that can negatively affect daily function, which may be improved with pulmonary rehabilitation. The meeting generated several key research questions related to cognitive-physical interactions in individuals with chronic lung diseases., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: D. R. reports financial support was provided by Canadian Institutes of Health Research, Sandra Faire and Ivan Fecan Professorship in Rehabilitation Medicine and Temerty Faculty of Medicine. W. D. R. reports financial support was provided by Canadian Institutes of Health Research and Canadian Lung Association. A. G. K. reports funding for advisory board or speakers bureau roles for AstraZeneca, Belus, Boehringer Ingelheim, Eisai, GSK, Idorsia, Merck Frosst, Moderna, Novo Nordisk, Pfizer, Respiplus, Sanofi, Teva, Trudel, and Valeo. D. D. M. is an outreach Editor for CHEST. M. A. S. reports grants from Netherlands Lung Foundation, Stichting Astma Bestrijding, Chiesi, AstraZeneca, TEVA, and Boehringer Ingelheim, outside the submitted work; and fees from Boehringer Ingelheim, GSK, and AstraZeneca, outside the submitted work that includes funding grants. M. K. S. is on the COPD Editorial Board for CHEST. None declared (P. C., J. L. C., G. D., P. W. D., H. E., J. H. F., J. A. G., D. Gold, R. S. G., D. Goodridge, T. J.-F., D. L., B. M., A. O.-C., J. O.-A., V. P., P. R., S. R., C. R., M. B. S., J. T., K. W.)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Importance: Identifying disparities in health outcomes related to modifiable patient factors can improve patient care., Objective: To compare likelihood of withdrawal of life-supporting treatment (WLST) and mortality in patients with complete cervical spinal cord injury (SCI) with different types of insurance., Design, Setting, and Participants: This retrospective cohort study collected data between 2013 and 2020 from 498 trauma centers participating in the Trauma Quality Improvement Program. Participants included adult patients (older than 16 years) with complete cervical SCI. Data were analyzed from November 1, 2023, through May 18, 2024., Exposure: Uninsured or public insurance compared with private insurance., Main Outcomes and Measures: Coprimary outcomes were WLST and mortality. The adjusted odds ratio (aOR) of each outcome was estimated using hierarchical logistic regression. Propensity score matching was used as an alternative analysis to compare public and privately insured patients. Process of care outcomes, including the occurrence of a hospital complication and length of stay, were compared between matched patients., Results: The study included 8421 patients with complete cervical SCI treated across 498 trauma centers (mean [SD] age, 49.1 [20.2] years; 6742 male [80.1%]). Among the 3524 patients with private insurance, 503 had WLST (14.3%) and 756 died (21.5%). Among the 3957 patients with public insurance, 906 had WLST (22.2%) and 1209 died (30.6%). Among the 940 uninsured patients, 156 had WLST (16.6%) and 318 died (33.8%). A significant difference was found between uninsured and privately insured patients in the adjusted odds of WLST (aOR, 1.49; 95% CI, 1.11-2.01) and mortality (aOR, 1.98; 95% CI, 1.50-2.60). Similar results were found in subgroup analyses. Matched public compared with private insurance patients were found to have significantly greater odds of hospital complications (odds ratio, 1.27; 95% CI, 1.14-1.42) and longer hospital stay (mean difference 5.90 days; 95% CI, 4.64-7.20), which was redemonstrated on subgroup analyses., Conclusions and Relevance: Health insurance type was associated with significant differences in the odds of WLST, mortality, hospital complications, and days in hospital among patients with complete cervical SCI in this study. Future work is needed to incorporate patient perspectives and identify strategies to close the quality gap for the large number of patients without private insurance.

Rationale: Prone positioning for ⩾16 hours in moderate-to-severe acute respiratory distress syndrome (ARDS) improves survival. However, the optimal duration of proning is unknown. Objectives: To estimate the effect of extended versus standard proning duration on patients with moderate-to-severe coronavirus disease (COVID-19) ARDS. Methods: Data were extracted from a five-hospital electronic medical record registry. Patients who were proned within 72 hours of mechanical ventilation were categorized as receiving extended (⩾24 h) versus standard (16-24 h) proning based on the first proning session length. We used a target trial emulation design to estimate the effect of extended versus standard proning on the primary outcome of 90-day mortality and secondary outcomes of ventilator liberation and intensive care unit (ICU) discharge. Analytically, we used inverse probability of treatment weighted (IPTW) Cox or Fine-Gray regression models. Results: A total of 314 patients were included; 234 received extended proning, and 80 received standard-duration proning. Patients who received extended proning were older, had greater comorbidity, were more often at an academic hospital, and had shorter time from admission to mechanical ventilation. After IPTW, characteristics were well balanced. Unadjusted 90-day mortality in the extended versus standard proning groups was 39% versus 58%. In doubly robust IPTW analyses, we found no significant effects of extended versus standard proning duration on mortality (hazard ratio [95% confidence interval], 0.95 [0.51-1.77]), ventilator liberation (subdistribution hazard, 1.60 [0.97-2.64], or ICU discharge (subdistribution hazard, 1.31 [0.82-2.10]). Conclusions: Using target trial emulation, we found no significant effect of extended versus standard proning duration on mortality, ventilator liberation, or ICU discharge. However, given the imprecision of estimates, further study is justified.

Introduction: Limited data exist on therapeutic ranges for newer antimicrobials in the critically ill, with few pharmacokinetic studies including patients undergoing renal replacement therapy or extracorporeal membrane oxygenation (ECMO)., Case Representation: These interventions can potentially alter the pharmacokinetic profile of antibiotics, resulting in therapeutic failures, antimicrobial resistance, or increased toxicity. In this report, we present two ECMO patients treated with cefiderocol and ceftobiprole, where therapeutic drug monitoring (TDM) aided in the successful treatment of severe infections. Antibiotic trough concentrations in both cases were consistent with previously reported therapeutic levels in critically ill and ECMO patients, meeting minimal inhibitory concentrations recommended by the European Committee on Antimicrobial Susceptibility Testing for the respective pathogens., Conclusion: Treatment might be suboptimal if doses are not adjusted based on physicochemical properties and extracorporeal support. In an era marked by highly resistant pathogens, these cases highlight the importance of timely access to real-time TDM for optimizing and individualizing antimicrobial treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: We sought to evaluate the effectiveness of any antiseizure medication on the incidence of early post-traumatic seizures among adult patients with traumatic brain injury., Data Sources: MEDLINE, Embase, PubMed, Cochrane Central Register of Controlled Trials, and LILACS were searched from inception to October 2023., Study Selection: We included randomized trials of adult patients with traumatic brain injury evaluating any antiseizure medication compared with either placebo or another agent., Data Extraction: Two reviewers independently extracted individual study data and evaluated studies for risk of bias using the Cochrane Risk of Bias tool. Our main outcome of interest was the occurrence of early seizures (i.e., within 7 d); secondary outcomes included late-seizures and all-cause mortality., Data Synthesis: Bayesian network meta-analyses were used to derive risk ratios (RRs) alongside 95% credible intervals (CrIs). We used Grading of Recommendations Assessment, Development, and Evaluation methodology to rate the certainty in our findings. Overall, ten individual randomized controlled trials (1851 participants) were included. Compared with placebo, phenytoin (RR, 0.28; 95% CrI, 0.13-0.57; moderate certainty) and levetiracetam (RR, 0.20; 95% CrI, 0.07-0.60; moderate certainty) were associated with a reduction in the risk of early seizures. Carbamazepine may be associated with a reduced risk of early seizures, but the evidence is very uncertain (RR, 0.41; 95% CrI, 0.12-1.27; very low certainty). Valproic acid may result in little to no difference in the risk of early seizures, but the evidence is very uncertain (RR, 0.97; 95% CrI, 0.16-9.00; very low certainty). The evidence is very uncertain about the impact of any antiseizure medication on the risk of late seizures or all-cause mortality at longest reported follow-up time., Conclusions: Phenytoin or levetiracetam reduce the risk of early seizures among adult patients with traumatic brain injury. Further research is needed to evaluate required duration of therapy and long-term safety profiles., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Purpose: Physical rehabilitation (PR) in the intensive care unit (ICU) may improve outcomes for survivors but clinical trial results have been discordant. We hypothesized that discordant results may reflect treatment heterogeneity received by "usual care" comparator groups in PR studies. Usual-care PR is typically underspecified, which is a barrier to comparing results across treatment studies. The primary objective of the present study was to describe the usual-care PR received by critically ill patients enrolled in the Canadian multicentre Critical Care Cycling to Improve Lower Extremity Strength (CYCLE) pilot randomized controlled trial (RCT) of PR. Other objectives were to help contextualize current research and provide data for international comparison., Methods: In this secondary analysis of the CYCLE pilot RCT, patients were randomized to in-bed cycling and usual-care PR or usual-care PR alone. Physiotherapists documented usual-care PR including therapy received, type of activity, duration, adverse events and consequences, reasons for no PR, and concurrent relevant medical interventions. We characterized usual care using descriptive statistics at the cohort and patient levels., Results: Across seven Canadian centres, 30 patients were randomized to usual-care PR. The median [interquartile range (IQR)] ICU stay was 10 [9-24] days and patients received PR on a median [IQR] of 5 [3-9] days for 23 [17-30] min per day. Eighteen patients (60%) stood, marched, or walked during usual care. Transient adverse events occurred in three patients on 1.5% (3/198) of days and none prompted session termination., Conclusions: In the usual-care arm of the CYCLE pilot RCT, PR was delivered on half of ICU days and over half of patients stood, marched, or walked. Adverse events during usual-care PR were uncommon., Study Registration: ClinicalTrials.gov ( NCT02377830 ); first posted 4 March 2015., (© 2024. Canadian Anesthesiologists' Society.)

Objectives: Hypothermic lung preservation at 10°C has recently shown to enhance quality of healthy donor lungs during ischemia. This study aims to show generalizability of the 10°C lung preservation using an endotoxin-induced lung injury with specific focus on the benefits of post-transplant lung function and mitochondrial preservation., Methods: Lipopolysaccharide (3 mg/kg) was injected intratracheally in rats to induce lung injury. Injured lungs were flushed with preservation solution and allocated to 3 groups (n = 6 each): minimum cold storage, 6-hour storage on ice (Ice), and 6-hour storage at 10°C (10C). Left lungs were transplanted and reperfused for 2 hours. After storage, lung tissue was used to evaluate the effects of hypothermic storage on the mitochondrial function: mitochondrial membrane potential was assessed by JC-1 staining; mitochondrial oxygen consumption was assessed using high resolution respirometry., Results: Two hours after reperfusion, the PO 2 /FiO 2 ratio from the graft was significantly higher in the 10C group than in the Ice group (P = 0.015), while the wet-to-dry weight ratio was significantly lower (P = 0.041). Levels of interleukin-8 in lung tissues were significantly lower in the 10C group than in the Ice group (P = 0.004). Mechanistically, we noted higher mitochondrial membrane potential and elevated state III respiration in the 10C group than in the Ice group (P = 0.015 and P = 0.002, respectively), implying higher metabolic activities may be maintained during 10°C preservation., Conclusions: Favorable metabolism during 10°C preservation prevented ischemia-induced mitochondrial damages in injured lungs, leading to better post-transplant outcomes., (Copyright © 2024. Published by Elsevier Inc.)

Background: Efficacy of inhaled therapy such as Nitric Oxide (iNO) during mechanical ventilation may depend on airway patency. We hypothesized that airway closure and lung collapse, countered by positive end-expiratory pressure (PEEP), influence iNO efficacy. This could support the role of an adequate PEEP titration for inhalation therapy. The main aim of this study was to assess the effect of iNO with PEEP set above or below the airway opening pressure (AOP) generated by airway closure, on hemodynamics and gas exchange in swine models of acute respiratory distress syndrome. Fourteen pigs randomly underwent either bilateral or asymmetrical two-hit model of lung injury. Airway closure and lung collapse were measured with electrical impedance tomography as well as ventilation/perfusion ratio (V/Q). After AOP detection, the effect of iNO (10ppm) was studied with PEEP set randomly above or below regional AOP. Respiratory mechanics, hemodynamics, and gas-exchange were recorded., Results: All pigs presented airway closure (AOP > 0.5cmH 2 O) after injury. In bilateral injury, iNO was associated with an improved mean pulmonary pressure from 49 ± 8 to 42 ± 7mmHg; (p = 0.003), and ventilation/perfusion matching, caused by a reduction in pixels with low V/Q and shunt from 16%[IQR:13-19] to 9%[IQR:4-12] (p = 0.03) only at PEEP set above AOP. iNO had no effect on hemodynamics or gas exchange for PEEP below AOP (low V/Q 25%[IQR:16-30] to 23%[IQR:14-27]; p = 0.68). In asymmetrical injury, iNO improved pulmonary hemodynamics and ventilation/perfusion matching independently from the PEEP set. iNO was associated with improved oxygenation in all cases., Conclusions: In an animal model of bilateral lung injury, PEEP level relative to AOP markedly influences iNO efficacy on pulmonary hemodynamics and ventilation/perfusion match, independently of oxygenation., (© 2024. The Author(s).)

Background: Patients with acute hypoxemic respiratory failure are at high risk of death and prolonged time on the ventilator. Interventions often aim to reduce both mortality and time on the ventilator. Many methods have been proposed for analyzing these endpoints as a single composite outcome (days alive and free of ventilation), but it is unclear which analytical method provides the best performance. Thus, we aimed to determine the analysis method with the highest statistical power for use in clinical trials., Methods: Using statistical simulation, we compared multiple methods for analyzing days alive and free of ventilation: the t, Wilcoxon rank-sum, and Kryger Jensen and Lange tests, as well as the proportional odds, hurdle-Poisson, and competing risk models. We compared 14 scenarios relating to: 1) varying baseline distributions of mortality and duration of ventilation, which were based on data from a registry of patients with acute hypoxemic respiratory failure and 2) the varying effects of treatment on mortality and duration of ventilation., Results and Conclusions: All methods have good control of type 1 error rates (i.e., avoid false positive findings). When data are simulated using a proportional odds model, the t test and ordinal models have the highest relative power (92% and 90%, respectively), followed by competing risk models. When the data are simulated using survival models, the competing risk models have the highest power (100% and 92%), followed by the t test and a ten-category ordinal model. All models struggled to detect the effect of the intervention when the treatment only affected one of mortality and duration of ventilation. Overall, the best performing analytical strategy depends on the respective effects of treatment on survival and duration of ventilation and the underlying distribution of the outcomes. The evaluated models each provide a different interpretation for the treatment effect, which must be considered alongside the statistical power when selecting analysis models., Competing Interests: Dr. Harhay is funded by the Patient-Centered Outcomes Research Institute (Award ME-2020C1-19220) and the U.S. National Institutes of Health/National Heart, Lung, and Blood Institute (grant numbers R00-HL141678 and R01-HL168202). Dr. Urner is supported by a Scholarship of the Interdepartmental Division of Critical Care Medicine, University of Toronto. Dr. Heath is funded by a Canada Research Chair in Statistical Trial Design; Natural Sciences and Engineering Research Council of Canada (award No. RGPIN-2021 03366). Dr. Goligher is funded by an Early Career Investigator Award from the National Sanitarium Association. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)